Demonstration of a positron beam-driven hollow channel plasma wakefield accelerator.

Plasma wakefield accelerators have been used to accelerate electron and positron particle beams with gradients that are orders of magnitude larger than those achieved in conventional accelerators. In addition to being accelerated by the plasma wakefield, the beam particles also experience strong transverse forces that may disrupt the beam quality. Hollow plasma channels have been proposed as a technique for generating accelerating fields without transverse forces. Here we demonstrate a method for creating an extended hollow plasma channel and measure the wakefields created by an ultrarelativistic positron beam as it propagates through the channel. The plasma channel is created by directing a high-intensity laser pulse with a spatially modulated profile into lithium vapour, which results in an annular region of ionization. A peak decelerating field of 230 MeV m(-1) is inferred from changes in the beam energy spectrum, in good agreement with theory and particle-in-cell simulations.

High-field plasma acceleration in a high-ionization-potential gas.

Plasma accelerators driven by particle beams are a very promising future accelerator technology as they can sustain high accelerating fields over long distances with high energy efficiency. They rely on the excitation of a plasma wave in the wake of a drive beam. To generate the plasma, a neutral gas can be field-ionized by the head of the drive beam, in which case the distance of acceleration and energy gain can be strongly limited by head erosion. Here we overcome this limit and demonstrate that electrons in the tail of a drive beam can be accelerated by up to 27 GeV in a high-ionization-potential gas (argon), boosting their initial 20.35 GeV energy by 130%. Particle-in-cell simulations show that the argon plasma is sustaining very high electric fields, of ∼150 GV m(-1), over ∼20 cm. The results open new possibilities for the design of particle beam drivers and plasma sources.

Multi-gigaelectronvolt acceleration of positrons in a self-loaded plasma wakefield.

Electrical breakdown sets a limit on the kinetic energy that particles in a conventional radio-frequency accelerator can reach. New accelerator concepts must be developed to achieve higher energies and to make future particle colliders more compact and affordable. The plasma wakefield accelerator (PWFA) embodies one such concept, in which the electric field of a plasma wake excited by a bunch of charged particles (such as electrons) is used to accelerate a trailing bunch of particles. To apply plasma acceleration to electron-positron colliders, it is imperative that both the electrons and their antimatter counterpart, the positrons, are efficiently accelerated at high fields using plasmas. Although substantial progress has recently been reported on high-field, high-efficiency acceleration of electrons in a PWFA powered by an electron bunch, such an electron-driven wake is unsuitable for the acceleration and focusing of a positron bunch. Here we demonstrate a new regime of PWFAs where particles in the front of a single positron bunch transfer their energy to a substantial number of those in the rear of the same bunch by exciting a wakefield in the plasma. In the process, the accelerating field is altered--'self-loaded'--so that about a billion positrons gain five gigaelectronvolts of energy with a narrow energy spread over a distance of just 1.3 metres. They extract about 30 per cent of the wake's energy and form a spectrally distinct bunch with a root-mean-square energy spread as low as 1.8 per cent. This ability to transfer energy efficiently from the front to the rear within a single positron bunch makes the PWFA scheme very attractive as an energy booster to an electron-positron collider.

High-efficiency acceleration of an electron beam in a plasma wakefield accelerator.

High-efficiency acceleration of charged particle beams at high gradients of energy gain per unit length is necessary to achieve an affordable and compact high-energy collider. The plasma wakefield accelerator is one concept being developed for this purpose. In plasma wakefield acceleration, a charge-density wake with high accelerating fields is driven by the passage of an ultra-relativistic bunch of charged particles (the drive bunch) through a plasma. If a second bunch of relativistic electrons (the trailing bunch) with sufficient charge follows in the wake of the drive bunch at an appropriate distance, it can be efficiently accelerated to high energy. Previous experiments using just a single 42-gigaelectronvolt drive bunch have accelerated electrons with a continuous energy spectrum and a maximum energy of up to 85 gigaelectronvolts from the tail of the same bunch in less than a metre of plasma. However, the total charge of these accelerated electrons was insufficient to extract a substantial amount of energy from the wake. Here we report high-efficiency acceleration of a discrete trailing bunch of electrons that contains sufficient charge to extract a substantial amount of energy from the high-gradient, nonlinear plasma wakefield accelerator. Specifically, we show the acceleration of about 74 picocoulombs of charge contained in the core of the trailing bunch in an accelerating gradient of about 4.4 gigavolts per metre. These core particles gain about 1.6 gigaelectronvolts of energy per particle, with a final energy spread as low as 0.7 per cent (2.0 per cent on average), and an energy-transfer efficiency from the wake to the bunch that can exceed 30 per cent (17.7 per cent on average). This acceleration of a distinct bunch of electrons containing a substantial charge and having a small energy spread with both a high accelerating gradient and a high energy-transfer efficiency represents a milestone in the development of plasma wakefield acceleration into a compact and affordable accelerator technology.

Beam loading by distributed injection of electrons in a plasma wakefield accelerator.

We show through experiments and supporting simulations that propagation of a highly relativistic and dense electron bunch through a plasma can lead to distributed injection of electrons, which depletes the accelerating field, i.e., beam loads the wake. The source of the injected electrons is ionization of the second electron of rubidium (Rb II) within the wake. This injection of excess charge is large enough to severely beam load the wake, and thereby reduce the transformer ratio T. The reduction of the average T with increasing beam loading is quantified for the first time by measuring the ratio of peak energy gain and loss of electrons while changing the beam emittance. Simulations show that beam loading by Rb II electrons contributes to the reduction of the peak accelerating field from its weakly loaded value of 43 GV/m to a strongly loaded value of 26 GV/m.

Transformation distances: a family of dissimilarity measures based on movements of segments.

MOTIVATION: Evolution acts in several ways on DNA: either by mutating a base, or by inserting, deleting or copying a segment of the sequence (Ruddle, 1997; Russell, 1994; Li and Grauer, 1991). Classical alignment methods deal with point mutations (Waterman, 1995), genome-level mutations are studied using genome rearrangement distances (Bafna and Pevzner, 1993, 1995; Kececioglu and Sankoff, 1994; Kececioglu and Ravi, 1995). The latter distances generally operate, not on the sequences, but on an ordered list of genes. To our knowledge, no measure of distance attempts to compare sequences using a general set of segment-based operations. RESULTS: Here we define a new family of distances, called transformation distances, which quantify the dissimilarity between two sequences in terms of segment-based events. We focus on the case where segment-copy, -reverse-copy and -insertion are allowed in our set of operations. Those events are weighted by their description length, but other sets of weights are possible when biological information is available. The transformation distance from sequence S to sequence T is then the Minimum Description Length among all possible scripts that build T knowing S with segment-based operations. The underlying idea is related to Kolmogorov complexity theory. We present an algorithm which, given two sequences S and T, computes exactly and efficiently the transformation distance from S to T. Unlike alignment methods, the method we propose does not necessarily respect the order of the residues within the compared sequences and is therefore able to account for duplications and translocations that cannot be properly described by sequence alignment. A biological application on Tnt1 tobacco retrotransposon is presented. AVAILABILITY: The algorithm and the graphical interface can be downloaded at http://www.lifl.fr/ approximately varre/TD

Detection of significant patterns by compression algorithms: the case of approximate tandem repeats in DNA sequences.

MOTIVATION: Compression algorithms can be used to analyse genetic sequences. A compression algorithm tests a given property on the sequence and uses it to encode the sequence: if the property is true, it reveals some structure of the sequence which can be described briefly, this yields a description of the sequence which is shorter than the sequence of nucleotides given in extenso. The more a sequence is compressed by the algorithm, the more significant is the property for that sequence. RESULTS: We present a compression algorithm that tests the presence of a particular type of dosDNA (defined ordered sequence-DNA): approximate tandem repeats of small motifs (i.e. of lengths < 4). This algorithm has been experimented with on four yeast chromosomes. The presence of approximate tandem repeats seems to be a uniform structural property of yeast chromosomes.

Compression and genetic sequence analysis.

A novel approach to genetic sequence analysis is presented. This approach, based on compression of algorithms, has been launched simultaneously by Grumbach and Tahi, Milosavljevic and Rivals. To reduce the description of an object, a compression algorithm replaces some regularities in the description by special codes. Thus a compression algorithm can be applied to a sequence in order to study the presence of those regularities all over the sequence. This paper explains this ability, gives examples of compression algorithms already developed and mentions their applications. Finally, the theoretical foundations of the approach are presented in an overview of the algorithmic theory of information.

Infective endocarditis due to Streptococcus bovis. A report of 53 cases.

Fifty-three patients (42 men; 11 women) with Streptococcus bovis infective endocarditis attended a tertiary cardiology hospital between 1980 and 1991, and constituted 11% of the total number of infective endocarditis cases hospitalized there during that period. The mean age was 59 +/- 15 years; 15 had previously suffered valvular disease (12) or had a valvular prosthesis (3); one patient had had a previous infective endocarditis. The infective episode involved the aortic valve in 26 patients, both the aortic and mitral valves in 18 patients, the mitral valve only in six and other valves in three. Echocardiographic examination showed one or more vegetations in 44 patients. Cardiac failure was diagnosed in 35 patients and embolic episodes in 22, of whom 11 were cerebrovascular accidents. The patients became afebrile 19 +/- 39 days after starting antibiotic treatment. Valve replacement was performed in 37 patients during their initial hospitalization, and in four during follow-up. After a mean follow-up of 4.6 +/- 3.1 years with a 100% follow-up, 15 patients died: 1 preoperatively, one in the first 30 days after operation, 13 later (8141 operated patients and 5/12 non-operated patients). Actuarial survival was 73% at 5 years. Gastrointestinal signs were present in 12 patients; 43 patients (81%) had a full colonic examination which showed polyps in 20 patients and adenocarcinomas in seven. Of 11 late deaths four were related to a malignant colonic tumour. This study confirms that Streptococcus bövis infective endocarditis is 'relatively benign', but it stresses the frequency and potential severity of the associated colonic lesions, requiring colonoscopy and making the treatment of high risk lesions mandatory.

[Recommendations for prevention of thromboembolism in heart valve diseases. Working Group on Valvular Heart Disease, European Society of Cardiology]. / Empfehlungen zur Thromboembolieprophylaxe bei Herzklappenerkrankungen der Working Group on Valvular Heart Disease, European Society of Cardiology.

Thromboembolic events are still a major cause of morbidity and mortality in patients with native valvular heart disease and in patients with prosthetic heart valves. Although the introduction of oral anticoagulation reduced this risk, thromboembolism and anticoagulation-related hemorrhages still represent significant problems in the management of these patients. In this article the guidelines developed by the Working Group on Valvular Heart Disease of the European Society of Cardiology for the management of antithrombotic therapy in heart valve disease are thoroughly discussed. The indication for and intensity of anticoagulation in various clinical situations, the concept of risk factor-adjusted intensity of anticoagulation, and the concept of control of oral anticoagulation with the International Normalized Ratio are presented.

[Has life expectancy of patients after surgery for aortic valve endocarditis improved over the last twelve years?]. / L'espérance de vie des malades opérés pour endocardite infectieuse aortique a-t-elle augmentée dans les douze dernières années?

Between 1983 and 1991, 104 patients (average age: 52 +/- 13 years) with aortic endocarditis (94 on native and 10 on prosthetic valves), were operated, 81 before the end of antibiotic therapy. Blood cultures were negative in 17 patients, identified a streptococcus in 49 patients, a staphylococcus in 16 patients, and a Gram negative or other organism in 22 patients. The following complications were observed before surgery: severe cardiac failure in 67 patients, renal failure in 24 patients, conduction defects in 13 patients, neurological complications in 13 patients, systemic or coronary embolism in 12 patients. Aortic valve replacement was performed in all patients, associated with mitral valve replacement in 25 patients and tricuspid valve replacement in 1 patient. Twelve patients died after surgery (11/81 of early operations, 1/23 operated later; NS). During a follow up of 3.5 +/- 2.8 years, there were 24 late deaths, 12 of non cardiovascular causes. Of the 20 variables tested, 3 were related to perioperative and late mortality (age, cardiac and renal failure). The 5 year survival (58.1 +/- 5.7%) is identical to that of the period 1970-1982 despite a very significant drop in perioperative mortality. Some of the causes of late mortality (older age of patients, changes in the infecting organisms) provide little hope of improving the prognosis in the near future. Others suggest that earlier surgery could improve the long term prognosis.

[Radionuclide ejection fraction at rest and in exercise in chronic aortic insufficiency. Pre- and postoperative study in asymptomatic or paucisymptomatic patients]. / Fraction d'éjection isotopique du ventricle gauche au repos et à l'effort dans l'insuffisance aortique chronique. Etude pré- et postopératoire chez les patients a- ou paucisymptomatiques.

Twenty patients (17 men and 3 women: average age 50 +/- 14 years) with asymptomatic or paucisymptomatic aortic regurgitation were studied to compare the values of radionuclide left ventricular ejection fraction (EF) at rest and on exercise before (1) and 6 +/- 1 months (2) and 5.7 +/- 1.1 years (3) after surgery. The resting EF was similar at all three examinations: 53 +/- 8 (1); 57 +/- 8 (2); 55 +/- 16 (3). However, it increased significantly on exercise from 40 +/- 10 (1) to 54 +/- 12 (2) (p < 0.001) and to 52 +/- 20 (3) (p = 0.036 versus 1). In the 7 patients with resting EF greater than 55 before surgery, there was no postoperative improvement: 61 +/- 6 (1); 61 +/- 5 (2); 65 +/- 9 (3). However, the exercise EF increased from 44 +/- 13 (1) to 55 +/- 17 (2) and 69 +/- 11 (3) (p = 0.004 vs 1). In 13 patients with resting EF < 55%, the value increased in the early postoperative phase but not later: resting: 49 +/- 5 (1); 55 +/- 8 (2) (p = 0.04); 49 +/- 17 (3) (NS vs 1); effort: 38 +/- 7 (1); 54 +/- 10 (2) (p < 0.001); 40 +/- 16 (3) (NS vs 1). Left ventricular systolic function only returns to normal and exercise after surgery in patients with resting preoperative EF > or = 55%, but nothing indicates that this normalisation is an absolute condition for a successful surgical result in aortic insufficiency in terms of survival and quality of life.

The risk of infective endocarditis after cardiac surgical and interventional procedures.

The risk of infective endocarditis after cardiac surgery relates mainly to the risk of infective endocarditis on prosthetic valves. The frequency of prosthetic infective endocarditis varies according to the criteria used in the literature, ranging from 0.4 to 1.3% for early infective endocarditis, with an annual linear risk of late infective endocarditis of 0.5%. This figure seems to be independent of either the type or the location of prostheses, but it does nevertheless increase if more than one valve has been replaced. The most commonly isolated microorganisms in early infective endocarditis are staphylococci. The bacteriological findings in late prosthetic infective endocarditis are similar to those seen in the native disease. The portal of entry is more easily identified in early than in late infective endocarditis (50%). The risk of infective endocarditis in surgically treated congenital heart disease is very low when the patient has a left-to-right shunt or valvar stenosis; it increases amongst patients with tetralogy of Fallot and patients with complex cyanotic congenital heart disease, mainly when there is a residual ventricular septal defect or prior palliative surgery. The risk of infective endocarditis in patients with intracavitary electrodes such as pacemakers and defibrillators, after the interventional procedure itself and after heart transplant, is very low. This leads us to conclude that antibiotic prophylaxis is only warranted in those patients with a prosthetic valve and after surgical treatment of tetralogy of Fallot and other complex cyanotic congenital heart diseases.

[Can irreversible ventricular dysfunction be identified in patients with heart valve disease?]. / Peut-on reconnaître les dysfonctions ventriculaires irréversibles chez les valvulaires?

Cardiologists and heart surgeons are often faced with the problem of the optimal therapeutic indication in patients with valvular heart disease presenting with severe myocardial dysfunction, as it is difficult to evaluate the degree of reversibility of a severe alteration of ventricular function in these patients. Myocardial dysfunction is often multifactorial in patients with valvular heart disease and the role of myocardial ischaemia secondary to associated coronary heart disease must not be neglected. On the other hand, the compensatory capacity of the myocardium varies from one patient to another ("constitutional" myocardial factor or related to the aetiology of the valvular heart disease?). Although the methods of investigation of myocardial function currently available are able to precisely evaluate the degree of severity of myocardial dysfunction, they are unable to accurately predict the degree of reversibility. 1. In pure mitral stenosis, severe left ventricular dysfunction is very rare; more or less rapidly, pulmonary hypertension induces slowly progressive right ventricular dysfunction which remains reversible for a long time. 2. In mitral incompetence, left ventricular systolic function is correctly evaluated by the ejection fraction (LVEF). There is a high risk of irreversible left ventricular dysfunction in operated patients with an LVEF of less than 0.40. In these patients, left ventricular function is slightly improved after mitral repair, while LVEF decreases after mitral valve replacement. The combined study of right ventricular systolic function is useful in patients with mitral disease, as this function may be insidiously altered and the presence of right heart failure, regardless of its cause, considerably increases the late postoperative mortality of mitral valve disease. 3. In aortic stenosis, left ventricular dysfunction, hypertrophy and interstitial fibrosis remain reversible for a long time. Severe alteration of LV function therefore does not exclude the possibility of very good postoperative recovery. However, this is improbable in the presence of: a very marked increase in LV mass and/or end-systolic volume, and/or inoperable associated coronary artery disease, and/or the combination of low ejection fraction, severely decreased cardiac output, and low transvalvular gradient (not increased by cautious dobutamine infusion), and/or clinical signs of complete heart failure. 4. In aortic incompetence, progressive alteration of left ventricular function, often asymptomatic, is reflected by the increased dimensions of the LV and a reduction of the fraction of ejection. The reversibility of LV dysfunction is difficult for evaluate. The long clinical course of this dysfunction is one of the most reliable predictors of irreversibility, together with a fall in the resting isotope LVEF.(ABSTRACT TRUNCATED AT 250 WORDS)

[Prognosis of non-revascularized triple coronary vessel disease. Apropos of 87 cases]. / Pronostic des coronariens tritronculaires non revascularisés. A propos de 87 observations.

Between 1982 and 1988, 87 patients (74 men, 13 women), with an average age of 59.6 +/- 10.1 years, had triple coronary artery disease and did not undergo any medical or surgical revascularisation, mainly because of the severity of the coronary disease or left ventricular dysfunction. Sixty-four patients had previous myocardial infarction, 33 unstable angina and 37 left ventricular failure. At coronary angiography, 31 patients had Class III or IV (NYHA) angina. The cardiothoracic ratio was 0.50 +/- 0.06; the left ventricular ejection fraction was 0.47 +/- 0.20. During follow-up of 3.9 +/- 2.6 years (2 patients lost to follow-up), 35 patients died (26 of cardiac and 9 of non-cardiac causes), giving a 5 year actuarial survival of 63%. In univariate analysis, the factors predictive of increased cardiac mortality were: absence of alcohol consumption (p = 0.013); class 3 or 4 angina (p = 0.017); resting angina (p = 0.030); cardiac failure (p = 0.0006); chest X ray showing interstitial or alveolar oedema (p = 0.002); increased cardiothoracic ratio (p = 0.003). A decreased left ventricular ejection fraction was only at the limit of statistical significance (p = 0.054). In multivariate analysis (Cox model), only 4 variables were correlated with increased cardiovascular mortality: resting angina (relative risk, RR = 2.56), cardiac failure (RR = 2.55), increased cardiothoracic ratio (RR = 2.14), absence of alcohol consumption (RR = 4.43). These results confirm the poor prognosis of patients with triple vessel disease not revascularised. They show the value of clinical appreciation to determine the prognosis of these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hypertrophic obstructive cardiomyopathy: current treatment, indications and results]. / Myocardiopathie hypertrophique obstructive: traitement actuel, indications et résultats.

Global annual mortality in hospitalized patients with symptomatic hypertrophic obstructive cardiomyopathy is just under 5%. Several treatments have been proposed for this severe disease in order to improve diastolic function and reduce the intraventricular obstacle. The aim is to improve symptomatology and prognosis. The mainstay of treatment is drug therapy. The negative inotrope and bradytrope action of beta-blockers given at medium doses of 160 to 320 mg/day (propranolol) helps decrease the incidence of dyspnoea chest pain and the frequency of syncopes in 30 to 70% of the patients. Higher doses up to 1 g per day may be helpful in certain patients, but with the risk of sudden death. Calcium channel inhibitors at a dose of 360 mg/day for verapamil give very favourable results in patients managed medically and sometimes in those undergoing surgery. Amiodarone is essentially used as an antiarrhythmic drug in obstructive syndromes complicated by severe ventricular arrhythmias. Wider use is limited due to cardiac and extracardiac side effects. Other drugs including disopyramide, diuretics, digitalics and antivitamin K agents also have a role to play. The aim of surgery is to alleviate the intraventricular obstacle, correct mitral regurgitation and increase left ventricular compliance. There has been much controversy over the most adapted approach, but the most commonly used technique is currently septal myectomy which reduces the intraventricular gradient by 80 to 90%. Simple mitral valve replacement gives similar improvement in cardiac haemodynamics but exposes the patient to the complications inherent with mitral prostheses. Dual chamber sequential pacing has also been proven to be an effective means of treating hypertrophic obstructive cardiomyopathy, reducing the risk of sudden death as well as symptomatology in selected patients. Apical pre-stimulation using a short atrio-ventricular delay and the paradoxical septal movement induced by right ventricular stimulation decreases the sub-aortic obstruction and thus improves left ventricular performance. This method must be confirmed by mid- and long term results. We are in agreement with the Mayo Clinic recommendations that surgical myectomy remains the preferred treatment for most patients with severe hypertrophic obstructive cardiomyopathy who are unresponsive to medical treatment.

[Pre- and postoperative ventricular arrhythmia in mitral valve insufficiency]. / Les arythmies ventriculaires pré- et postopératoires de l'insuffisance mitrale.

In order to assess the prevalence and prognosis of ventricular arrhythmias in patients with surgical mitral regurgitation, a prospective cooperative study was undertaken in 14 French cardiological centres. Seventy-nine patients (45 men, 34 women, average age 62.8 +/- 12.8 years), who underwent mitral valvuloplasty (44 cases) or valve replacement (35 cases), were included. Three 24 hour Holter recordings were performed before, 15 days and 6 months after surgery. Etiology of mitral disease was dystrophic in 49 patients, degenerative in 11, rheumatic in 10, post-endocarditis in 3 and undetermined in 6. Only 5 patients had a left ventricular ejection fraction < or = 45 %. Complex ventricular arrhythmias (Lown > or = 4) were recorded before surgery in 22 patients (28 %), more often in dystrophic disease (17/49 versus 5/30, p = 0.04). No significant correlation was observed between the ventricular arrhythmias and the other preoperative findings, except for a tendency to an inverse correlation between the left ventricular ejection fraction and the Lown grade. Two patients died in the immediate postoperative period (Lown 1); 1 died of a non-cardiac cause at the 2nd month (Lown 4A). The prevalence of complex arrhythmias was unchanged after surgery (34 % on early Holter and 22% on late Holter recordings) with no difference between valvuloplasty and valve replacement. In conclusion, these results indicate that ventricular arrhythmias do not influence the early and 6 month postoperative prognosis in mitral regurgitation with good left ventricular function.